miR-1靶向LXRα调控糖尿病心肌中脂质代谢的作用及其机制研究

项目名称： miR-1靶向LXRα调控糖尿病心肌中脂质代谢的作用及其机制研究

项目编号： No.81500629

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 成永霞

作者单位： 牡丹江医学院

项目金额： 18万元

中文摘要： 糖尿病心肌病是独立于高血压、冠心病以及动脉粥样硬化的特异性心肌病变，是糖尿病患者死亡的主要原因之一。糖脂代谢紊乱导致的心肌功能改变是糖尿病心肌病的始动因素，但其病理机制仍需进一步研究。申请人首次在糖尿病心肌病大鼠模型中发现与多种体内能量代谢密切联系的LXRα及相关基因在心肌组织中的异常表达，体外实验中也发现LXR激动剂可能拮抗高糖所致的心肌细胞损伤，预示LXRα在糖尿病心肌病发生发展过程中的重要作用。miR-1能够靶向调控LXRα的表达，且其可能参与了对糖尿病心肌病发展的调控。本项目拟采用基因沉默、miRNA转染、Western blot等技术，从体内及体外两个方面探讨miR-1靶向调控LXRα在心肌脂质代谢以及糖尿病心肌病发展中的作用及其机制，旨在为糖尿病心肌病发病机制的研究提供更多的实验依据，尽可能为糖尿病心肌病的预防及治疗提供新的靶点。

中文关键词： 糖尿病心肌病；肝X受体α；脂质代谢；miR-1

英文摘要： Diabetic cardiomyopathy (DCM) is a specific cardiomyopathy independent of hypertension, coronary disease and atherosclerosis. It is one of the main causes of death in diabetic patients. Myocardial dysfunction caused by disturbance in the lipid and glucose metabolism is an initial factor resulting in diabetic cardiomyopathy, but the pathogenesis needs further research. Our previous research has found that the expression of LXRα, which closely associated with body energy metabolism, has a abnormal change in the cardiac muscular of DCM rat. Also, our studies have shown that LXR agonists may attenuate the cellular damage of myocardial induced by high glucose in vitro. We have a sufficient reason to speculate that LXRα plays an important role in the occur and develop progress in DCM. MiR-1 can regulate the expression of LXRα by the targeting effect, and it may take part in regulation of the development of DCM. This project intends to use methods such as gene silencing, miRNA transfection, Western blot to investigate the effects and mechanism of miR-1 on the lipid metabolism and disease development in diabetic cardiomyopathy by targeting LXRα in vitro and in vivo. This study is designed to provide further experimental bases for the research of the pathogenesis of DCM and a new therapeutic targets is expected to offered.

英文关键词： Diabetic cardiomyopathy;LXRα;Lipid metabolism;miR-1